1. Field of the Invention
This invention relates to substituted 2-(4-benzylpiperazin-1-yl) and 2-(1-benzylpiperidin-4-yl)ethanones and to pharmaceutical compositions containing such compounds. It also relates to the use of such compounds in the treatment or prevention of psychotic disorders such as schizophrenia and other central nervous system diseases.
2. Description of the Related Art
The therapeutic effect of conventional antipsychotics, known as neuroleptics, is generally believed to be exerted through blockade of dopamine receptors. However, neuroleptics are frequently responsible for undesirable extrapyramidal side effects (EPS) and tardive dyskinesias, which are attributed to blockade of D.sub.2 receptors in the striatal region of the brain. The dopamine D.sub.4 receptor subtype has been identified (Nature, 347: 146 (Sokoloff et al., 1990)). Its unique localization in limbic brain areas and its differential recognition of various antipsychotics suggest that the D.sub.4 receptor may play a major role in the etiology of schizophrenia. Selective D.sub.4 antagonists are considered effective antipsychotics free from the neurological side effects displayed by conventional neuroleptics.
Various 4-benzylpiperazines have been described. See, for example, Arch. Med. Res., 25: 435-440 (Terron et al., 1994) and Toxicol. Appl. Pharmacol., 7: 257-267 (Schmidt and Martin, 1965).